Antiseptic compress

ABSTRACT

The invention concerns an antiseptic compress comprising a contact surface with the wound or burn, consisting of an elastomeric matrix highly plasticized with a non-polar oil or grease, said elastomeric matrix containing a dispersed hydrocolloid. The invention is characterised in that said elastomeric matrix further comprises likewise dispersed at least an antiseptic agent and at least a surfactant whereof the hydrophilic/lipophilic balance (HLB) is higher than 10. The invention is applicable in particular to compresses and dressings.

[0001] The present invention relates to an antiseptic compress forpromoting the healing of infected wounds or wounds susceptible toinfection, and to a dressing incorporating the antiseptic compress.

PRIOR ART

[0002] It is already known that dressings capable of maintaining acertain moisture level on the surface of a wound have a favorable actionon the healing process. This property is utilized in numerous dressings,for example “ALGOPLAQUE” marketed by Laboratoires URGO or “COMFEEL”marketed by COLOPLAST, which use a dispersion of hydrocolloids in anadhesive hydrophobic matrix; in these dressings the hydrocolloidparticles absorb the exudates and maintain a moist environment favorableto healing. However, in the case of highly exudative wounds, theabsorption is inadequate and it is possible to observe an accumulationof fluids which are likely rapidly to become a focus of infection.

[0003] Another type of dressing, known as a tulle gras, uses greases andoils, such as officinal petrolatum and paraffin, to form a woundprotection. Absorption of the exudates is not possible here and acompress has to be provided in the case of weeping wounds. In othercases the wound tends to dry and adhesions are then frequently observedbetween the dressing and the freshly regenerated tissues. This entailspainful renewal of the dressing, if not destruction of the scar tissues.To avoid the problems of infection in wounds, it is known to addantiseptics to the dressing in order to limit or, preferably, reduce thedevelopment of infectious pathogens. Dressings are known in this fieldwhich contain antiseptics dispersed in an ointment based on hydrophobicfats, an example of such a dressing being UNITUL marketed by BAMA-GEVE.Also, EP-A-689425 discloses a hydrating gel comprising a hydrocolloidsystem based on alginate and sodium carboxymethyl cellulose and apreservative system consisting of antimicrobials and antifungals. Saidgel is a hydrogel containing a high proportion of water (97%), in whichthe active agents are in solution. A similarly formulated dressing withthe mark CONNETIVINA PLUS, marketed by FIDIA, is also known; thisconsists of a hydrogel based on polyethylene glycol and contains silversulfadiazine in dispersion and a hyaluronic acid salt.

[0004] FR 2 775 903 is also known and describes an adhesive hydrocolloidmass for dressings, the absorption capacity of which is amplified andaccelerated by the combined presence of a hydrocolloid and a surfactant.This adhesive mass can additionally contain an antiseptic, which caneasily be diffused when the dressing has absorbed an aqueous fluidcapable of partially dissolving said antiseptic.

[0005] In the case of dressings which have a hydrophobic contact layerbased especially on fats or elastomers, it is much more difficult toobtain an antiseptic action by means of active substances dispersed inthe contact layer. These active substances are trapped in thehydrophobic structure and therefore possess an extremely lowbioavailability. This problem is exacerbated when using poorly absorbentor non-absorbent dressing structures comprising fairly cohesiveelastomers in order to prevent the dressing structure from breaking downwhen the dressing is removed from the wound. For this reason there areno dressings at the present time which contain both synthetic elastomersand antiseptics in a non-adhesive and non-absorbent contact layer.

SUBJECT OF THE INVENTION

[0006] The aim of the present invention is to provide a non-adhesive andpoorly absorbent contact compress for skin wounds or burns susceptibleto infection, said compress being based on fats and hydrocolloids, and adressing incorporating such a compress.

DESCRIPTION

[0007] It has been found according to the invention that it is possibleto obtain a compress consisting of a non-adhesive, amphiphilic, cohesivecontact layer and having an antiseptic action. It has in fact been foundthat the bioavailability of the antiseptics dispersed in the contactlayer can be considerably improved in the presence of a non-ionicsurfactant with a hydrophilic/lipophilic balance (HLB) greater than 10.

[0008] The compress according to the invention, consisting of a cohesivestructure based on synthetic elastomers of the tri-block type highlyplasticized with a non-polar oil, is characterized in that it contains,in dispersion, a small amount of hydrocolloids, at least one antisepticand at least one surfactant with a hydrophilic/lipophilic balance (HLB)greater than 10.

[0009] According to one particular feature of the invention, thesynthetic elastomers are tri-block elastomers with a saturated centralblock, such as a copolymer of polystyrene blocks andpolyethylene-butylene blocks (SEBS) or a copolymer of polystyrene blocksand polyethylene-propylene blocks (SEPS).

[0010] According to another particular feature of the invention, thenon-polar oil is a paraffin oil, an officinal petrolatum or a mixture ofthese compounds.

[0011] According to another particular feature of the invention, thehydrocolloids are present in the form of sodium carboxymethyl cellulose(CMC).

[0012] According to another particular feature of the invention, thesurfactant is of the non-ionic type and is selected from polyethoxylatedderivatives of sorbitol fatty acid esters.

[0013] According to another particular feature of the invention, theantiseptics are antimicrobial active substances and/or antifungal activesubstances preferably selected from silver salts.

[0014] In a preferred embodiment of the invention, the wound-contactinglayer is discontinuous and preferably consists of an open-mesh wovenfabric totally coated with a non-adhesive cohesive gel so as to leavethe meshes essentially unobstructed, said gel being formed of a highlyplasticized, hydrophobic elastomeric matrix containing a dispersion ofhydrocolloids, at least one antiseptic and at least one surfactant witha hydrophilic/lipophilic balance (HLB) greater than 10.

DETAILED DESCRIPTION

[0015] The antiseptic compress according to the invention comprises awound-contacting layer essentially consisting of a non-adhesive cohesiveGel in which hydrocolloids, one or more antiseptics and a surfactantwith a hydrophilic/lipophilic balance (HLB) greater than 10 aredispersed.

[0016] The cohesive gel, which serves to constitute the structure of thecontact layer and assure the non-adhesive character of the dressing,consists of an elastomeric matrix, preferably based on tri-blockelements, associated with a large amount of a non-polar oil or fat whichwill act simultaneously as plasticizer for the elastomeric material andas antiadhesive. This produces a non-adhesive cohesive gel which is veryelastic, very easily shaped and very resistant to tearing.

[0017] It is preferable to use elastomers of the high molecular weightSEBS or SEPS type, for example those marketed by SHELL under thereference Kraton G 1651 or by KURARAY under the name SEPTON. Theseelastomers are present in the contact layer in an amount of about 3 to8% by weight.

[0018] By specifically choosing these tri-block elastomers, it ispossible to obtain a gel which is devoid of adhesiveness and perfectlyantiadhesive towards the regenerated tissues and perilesional skin.

[0019] The non-polar oil is generally a mineral oil or mixture ofmineral oils based on hydrocarbons, which can be fluid or more or lessthick.

[0020] Within the framework of the invention, it will be preferable touse a paraffin oil, an officinal petrolatum or a mixture of thesecompounds.

[0021] It will be particularly preferable to use one or more mineraloils marketed by SHELL under the name ONDINA, preferably under thereference ONDINA 15, either alone or, advantageously, in a mixture withan officinal petrolatum as defined in the French pharmacopeia.

[0022] The non-polar oil is present in an amount of about 55 to 90% ofthe weight of the contact layer.

[0023] The compress also comprises a small amount of hydrocolloids indispersion in the elastomeric matrix, a preferred hydrocolloid beingsodium carboxymethyl cellulose (CMC), the function of which is tomaintain a moist environment favorable for the healing process. In thecase where sodium CMC is used, it is present in the form of a finepowder with a particle size of about 50 to 100 μm, in an amount of about3 to 20%, preferably of about 4 to 14%, of the weight of the contactlayer. Although small, this amount of hydrocolloid is sufficient tomaintain a moisture level on the surface in contact with the woundwithout making the compress very absorbent, and makes it possible toprevent the contact layer from swelling.

[0024] In particular, the compresses according to the invention have anegligible or very low absorption capacity towards aqueous fluids andthe increase in weight when they are brought into contact with water isminimal, being generally less than 50% and preferably less than 25% ofthe weight of the contact layer.

[0025] Within the framework of the invention, other hydrocolloids, forexample alginates, can be used instead of CMC.

[0026] The contact layer also contains antiseptics in dispersion in theelastomeric material. The chosen active substances are those known fortheir antimicrobial or antifungal properties, especially compounds whichare active in combating the development of pathogenic germs, for exampleStaphylococcus aureus (golden staphylococcus) or Pseudomonas aeruginosa(pyocyanic organism).

[0027] Among these active substances, which can be used alone or incombination, preference is given to chlorhexidine, hexamidine, betadineor silver salts such as silver sulfadiazine, silver chloride or silvernitrate. The amount present in the contact layer depends on the natureof the active principle and varies between 0.2 and 5%.

[0028] According to the invention, at least one surfactant is added inorder to ensure that the resulting activity of the antiseptic iscorrect. The chosen surfactant is a non-ionic surfactant with ahydrophilic/lipophilic balance (HLB) greater than 10, preferably greaterthan 14, i.e. one predominantly of distinctly hydrophilic character.This surfactant must preferably be present in an amount of 1 to 6% byweight in the formulation. Among the commercially available productssuitable for carrying out the invention, preference is given e.g. topolyethoxylated sorbitol esters, especially the polysorbate 80 availableunder the reference Montanox 80 from SEPPIC, which has ahydrophilic/lipophilic balance (HLB) of about 15 to 16.

[0029] Conventionally the formulation also comprises additives forensuring the stability of the product, examples being antioxidants orphotoprotective agents.

[0030] The elastomeric mass constituting the contact layer of thecompress is produced by a hot-melt process in which the variousconstituents are mixed hot, the hydrocolloid and the active substancebeing added after a homogeneous mixture of the elastomers and the oilyplasticizer has been obtained. The resulting mixture is then coated ontoa flexible substrate which is easily shaped, for example a film or anon-woven or woven fabric, to give a dressing applicable directly to theskin.

[0031] In one of the preferred embodiments of the invention, the moltenmixture can also be coated onto a wide-mesh woven fabric so that thethreads constituting the fabric are totally coated and the meshapertures are left unobstructed. The woven fabric used to produce thisnovel compress is preferably composed of synthetic threads with longfibers. This gives a discontinuous layer reinforced by the net, which isvery easily shaped and which combines properties favorable to healingwith the antiseptic property.

[0032] This antiseptic compress, which is used analogously to a tullegras, can be brought into direct contact with a wound or burn, coveredwith an absorbent pad and held with tape or adhesive.

[0033] By way of example, a compress (El) was produced from anelastomeric mass prepared by the hot-melt process from 1.52 kg ofparaffin oil (obtained from SHELL under the reference ONDINA 15), 100 gof high molecular SEBS elastomer (Kiaton G 1651 marketed by SHELL), 100g of officinal petrolatum, 2.5 g of phenolic antioxidant, 300 g offinely powdered sodium carboxymethyl cellulose (ref. 7H4XF marketed byAQUALON), 100 g of polysorbate 80 (marketed under the reference MONTANOX80 by SEPPIC) and 60 g of finely powdered silver sulfadiazine (of USPgrade). The molten mass was coated onto an open-mesh woven fabric of themarquisette type made of 33 dtex polyester threads and having squaremeshes with an aperture of about 1 mm². The fabric is coated by passagethrough a bath of the molten elastomeric mass at 135-145° C. after whichthe excess gel is removed by rolling between two cylinders. The strip ofcoated fabric is quickly cooled in a stream of cold air. The amount ofgel deposited on the threads is about 145 g/m², which corresponds toabout 4 g m² of silver sulfadiazine. The strip obtained is subsequentlylaminated with a protective film of opaque polyester on each side, thencut into fragments of appropriate size for use as a compress, andfinally packaged in a leaktight sachet.

[0034] The antiseptic character of the compress (El) according to theinvention, produced above, was tested in vitro by contact with a culturemedium. The following were used for comparison in this study:

[0035] a) a control compress (A) whose formulation is analogous to thatof the compress (E1) above except that it contains neither activeprinciple nor surfactant;

[0036] b) a compress (B) whose formulation is analogous to that of thecompress (E1) and contains the active principle (i.e. 2.75% of silversulfadiazine) but no surfactant; and

[0037] c) a compress (C) of a type analogous to that described as thecontrol (A). i.e. without active principle or surfactant, on which a 3mm layer of Flammazine gel has been deposited, this method being commonpractice in hospitals. Flammazine is an emulsified cream containing 1%of silver sulfadiazine.

[0038] The tests were performed on two bacterial strains: Staphylococcusaureus and Pseudomonas aeruginosa. which are frequently responsible fornosocomial infections and/or superinfections in major burns. Disks 10 mmin diameter are cut out of each of the compresses to be tested and aredeposited on geloses which have been inoculated in the bulk or on thesurface with a bacterial suspension of known titer. After incubation for24 hours at 37° C., the diameters of the zones of bacterial growthinhibition are measured and compared.

[0039] This experiment used trypcase-soya gelose (G1) or Mueller-Hinton2 gelose (G2) (both supplied by BIOMERIEUX), which were inoculated inthe bulk with 1 ml of a bacterial suspension with a titer of about 10⁹or 10⁶ CFU/ml per 15 to 18 ml of gelose, or on the surface with 1 ml ofa bacterial suspension with a titer of about 10⁸ CFU/ml (CFU=ColonyForming Unit). The results obtained, represented by the diameter of theinhibition zones expressed in mm, are shown in Tables 1 to 3. TABLE 1Pseudomonas aeruginosa 10⁹ CFU/ml G1 G2 Compress bulk surface bulksurface A 10 10 10 10 B 10 10 10.5 10.5 C 13 12 12 11 E1 15 13 15 14

[0040] TABLE 2 Staphylococcus aureus 1.2.10⁹ CFU/ml G1 G2 Compress bulksurface bulk surface A 10 10 10 10 B 10 11 10 10 C 12 12 11 10 E1 11 1412 10.5

[0041] TABLE 3 Mueller Hinton 2 gelose inoculated in the bulkPseudomonas Staphylococcus aeruginosa aureus 2.9 × 10⁶ CFU/ml 2.1 × 10⁸CFU/ml A 10 10 B 10.5 11.5 C 17 16.5 E1 17 16

[0042] In the above Tables, a result of 10 denotes that no zone aroundthe compress disk of diameter 10 mm is devoid of bacterial growth.

[0043] Results above 10 denote that a peripheral zone around thecompress is devoid of bacterial growth.

[0044] Table 1 relates to inhibition of the growth of Pseudomonasaeruginosa on the two types of gelose inoculated in the bulk or on thesurface at a concentration of the order of 10⁹ CFU/ml. Table 2 relatesto the same type of experiment performed with Staphylococcus aureus.Table 3 relates to inhibition of the growth of both bacterial strains atconcentrations of the order of 10⁶ CFU/ml.

[0045] As expected, the results obtained show a total inactivity of thecompress devoid of active substance (A), a very weak antiseptic activityof the compress containing the active substance but no surfactant, and agood inhibition of bacterial growth in the presence of the compressaccording to the invention (E1), the inhibition obtained generally be atleast equivalent to that obtained in the presence of the compressassociated with a thick layer of Flammazine. The results also confirmthe need for the presence of a surfactant of hydrophilic type in orderto make the antiseptic bioavailable at the surface to be renderedaseptic.

[0046] The absorption capacity of a contact layer produced with theelastomeric mass according to the above Example was measured andcompared with an adhesive hydrocolloid mass such as that described indocument FR 2775903. A continuous layer of the mixture formulatedaccording to Example E1 of the present invention, weighing about 600g/m², was produced for this test. The Comparative Example corresponds tothe absorbent adhesive mass according to Example 1 of document FR2775903, weighing 350 g/m². To measure the absorption capacity, a 25 cm²sample of each of the products was immersed for one hour in isotonicsolution kept at 37° C. When the immersion time had elapsed the sampleswere drained and weighed. The weight increases calculated from theseresults show an absorption capacity of 144 g/m² for the Exampleaccording to the present invention and 1575 g/m² for the ComparativeExample. Expressed as percentages by weight, the weight increases arerespectively 144/600=24% for the Example according to the invention and1575/350=450% for the Comparative Example.

[0047] The dressings obtained using a compress according to theinvention thus have numerous advantages for the treatment of wounds orburns accompanied by a risk of infection: their composition makes itpossible simultaneously to obtain a non-adhesive greasy contact throughthe presence of an oil or petrolatum, a moist environment through thepresence of a hydrocolloid, and an aseptic medium created by asufficient diffusion of an antiseptic. Furthermore, the structure of theelastomeric layer, which forms the contact layer together with the otheringredients, enables the dressing to be handled easily and removedgently and painlessly without leaving material originating from thecontact layer on the newly regenerated tissues.

1. Compress for the treatment of wounds or burns, whose contact surface with the wound or burn consists of an elastomeric matrix plasticized with a non-polar oil, said elastomeric matrix containing a hydrocolloid in dispersion, characterized in that said elastomeric matrix also contains, in dispersion, at least one antiseptic and at least one surfactant with a hydrophilic/lipophilic balance (HLB) greater than 10, said non-polar oil representing 55 to 90% of the weight of the compress.
 2. Compress according to claim 1, characterized in that the structure of the elastomeric matrix consists of a synthetic elastomer of the tri-block type, preferably of the tri-block type with a saturated central block, selected from high molecular copolymers of polystyrene blocks and polyethylene-butylene blocks (SEBS) and high molecular weight copolymers of polystyrene blocks and polyethylene-propylene blocks (SEPS).
 3. Compress according to claim 1 or 2, characterized in that the non-polar oil is selected from paraffin oils, officinal petrolatum and mixtures of these compounds.
 4. Compress according to one of claims 1 to 3, characterized in that the hydrocolloid is sodium carboxymethyl cellulose.
 5. Compress according to one of claims 1 to 4, characterized in that the surfactant is of the non-ionic type and is selected from polyethoxylated derivatives of sorbitol fatty acid esters.
 6. Compress according to one of claims 1 to 5, characterized in that the antiseptic is a silver salt.
 7. Compress according to any one of claims 1 to 6, characterized in that the surface in contact with the wound is in the form of a discontinuous layer which has been coated onto a wide-mesh woven substrate in such a way as to coat the threads of the fabric totally and leave the mesh apertures essentially unobstructed.
 8. Dressing obtained with a compress according to any one of claims 1 to 7, characterized in that said compress is placed on a substrate consisting of a film or a flexible nonwoven fabric capable of being rendered adhesive. 